Clinical Policy: Infertility Therapy Reference Number: CP.CPA.261 Effective Date: 11.16.16 Last Review Date: 11.17 Line of Business: Medicaid – Medi-Cal Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are gonadotropins requiring prior authorization: Menotropins (Menopur®), Follitropin alpha, recombinant (Gonal-F® RFF), Follitropin beta, recombinant (Follistim®-AQ), Urofollitropin (Bravelle®), Choriogonadotropin alfa (Ovidrel®), Human chorionic gonadotropin (Novarel®, Pregnyl®), Ganirelex acetate, Cetrorelix (Cetrotide®). FDA approved indication Menopur is indicated for development of multiple follicles and pregnancy in ovulatory women as part of an Assisted Reproductive Technology (ART) cycle. Gonal-F RFF is indicated: • For induction of ovulation and pregnancy in oligo-anovulatory women in whom the cause of infertility is functional and not due to primary ovarian failure. • For development of multiple follicles in ovulatory women as part of an Assisted Reproductive Technology (ART) cycle. Follistim AQ is indicated: • In women for: Induction of ovulation and pregnancy in anovulatory infertile women in whom the cause of infertility is functional and not due to primary ovarian failure. • In women for: Pregnancy in normal ovulatory women undergoing controlled ovarian stimulation as part of an In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycle. • In men for: Induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism (HH) in whom the cause of infertility is not due to primary testicular failure. Bravelle is indicated: • For induction of ovulation in women who have previously received pituitary suppression. • For development of multiple follicles as part of an Assisted Reproductive Technology (ART) cycle in ovulatory women who have previously received pituitary suppression. Ganirelix is indicated for inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation. Cetrotide is indicated for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation. Page 1 of 6 CLINICAL POLICY Infertility Therapy Ovidrel is indicated: • For induction of final follicular maturation and early luteinization in infertile women who have undergone pituitary desensitization and who have been appropriately pretreated with follicle-stimulating hormones (FSH) as part of an Assisted Reproductive Technology (ART) program such as in vitro fertilization and embryo transfer. • For induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary ovarian failure. Novarel and Pregnyl are indicated: • For prepubertal cryptorchidism not due to anatomic obstruction. • For selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males • For induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately pretreated with human menotropins. Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation® that Menopur, Gonal-F RFF, Follistim-AQ, Bravelle, Ovidrel, Novarel, Pregnyl, Ganirelex acetate, and Cetrotide are medically necessary when the following criteria are met: I. Initial Approval Criteria A. All Indications (must meet all): 1. Prescribed for one of the following a. Induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not caused by primary ovarian failure; b. To stimulate the development of multiple follicles in ovulatory patients undergoing Assisted Reproductive Technology (ART), e.g., in vitro fertilization; c. Induction of final follicular maturation and early luteinization in infertile women who have undergone pituitary desensitization and who have been appropriately pretreated with follicle stimulating hormones (FSH) as part of an Assisted Reproductive Technology (ART) program; d. Inhibition of premature luteinizing hormone in women undergoing controlled ovarian hyperstimulation; e. Induction of ovulation in women with primary hypothalamic amenorrhea; f. For Follistim AQ only: i. Pregnancy in normal ovulatory women undergoing controlled ovarian stimulation as part of an In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycle; ii. In men: the induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism (HH) in whom the cause of infertility is not due to primary testicular failure; Page 2 of 6 CLINICAL POLICY Infertility Therapy g. For Novarel, Pregnyl only: i. Prepubertal cryptorchidism not due to anatomical obstruction; ii. Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males. Approval duration: Length of Benefit B. Other diagnoses/indications 1. Refer to CP.PHAR.57 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). II. Continued Therapy A. All Indications (must meet all): 1. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; 2. Member is responding positively to therapy. Approval duration: Length of Benefit B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via Centene benefit and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.PHAR.57 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off-label use policy – CP.PHAR.57 or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ART: Assisted Reproductive Technology ICSI: Intracytoplasmic Sperm Injection FSH: follicle-stimulating hormones IVF: In Vitro Fertilization HH: hypogonadotropic hypogonadism LH: luteinizing hormone Appendix B: General Information N/A Appendix C: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/ Maximum Dose Various Depending on patient's diagnosis and Varies previous therapy Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Page 3 of 6 CLINICAL POLICY Infertility Therapy V. Dosage and Administration Drug Name Dosing Regimen Maximum Dose Menopur (menotropins) Various, see package insert Varies Gonal-F RFF (follitropin alpha, Various, see package insert Varies recombinant) Follistim-AQ (follitropin beta, Various, see package insert Varies recombinant) Bravelle (urofollitropin) Various, see package insert Varies Ovidrel (choriogonadotropin alfa) Various, see package insert Varies Novarel, Pregnyl (human chorionic Various, see package insert Varies gonadotropin) Ganirelex acetate Various, see package insert Varies Cetrotide (cetrorelix) Various, see package insert Varies VI. Product Availability Drug Availability Menopur Injection: 75 U FSH and 75 U LH/vial Gonal-F multi dose vial Injection: 450 U/vial; 1,050 U/vial Gonal-F RFF single dose vial: Injection: 75 U/vial Gonal-F RFF Redi-ject Prefilled auto-injection device: 300 U/0.5 mL, 450 U/0.75 mL, 900 U/1.5 mL Follistim-AQ Injection: 75 U/0.5 mL Injection cartridge: 300 U, 600 U, 900 U Bravelle Injection: 75 U FSH/vial Ovidrel Prefilled Syringe: 250 mcg/0.5 mL Chorionic gonadotropin Injection: 10,000 U/vial Novarel Injection: 10,000 U/vial Pregnyl Injection: 10,000 U/vial Ganirelex acetate Prefilled Syringe: 250 mcg/0.5 mL Cetrotide (cetrorelix) Injection: 0.25 mg/vial VII. References 1. Micromedex® Healthcare Series [Internet database]. Greenwood Village, CO: Thompson Helathcare. Updated periodically. Accessed February 28, 2016. 2. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed February 28, 2016. 3. Health Net National Medical Policies, Infertility, April 2011. https://hnconnect.healthnet.com/business_units/medical_management/national_medical_poli cies/list.jsp Accessed February 28, 2016. 4. Gonal-F RFF [Prescribing Information] Rockland, MA: EMD Serono; January 2017. 5. Follistim AQ [Prescribing Information] Ravensburg, Germany: Vetter Pharma-Fertigung GmbH & Co. KG; December 2014. 6. Menopur [Prescribing Information] Parsippany, NJ: Ferring Pharmaceuticals; July,2016. 7. Bravelle [Prescribing Information] Parsippany, NJ: Ferring Pharmaceuticals; February 2014. 8. Ovidrel [Prescribing Information] Rockland, MA: EMD Serono; September 2014. 9. Novarel [Prescribing Information] Parsippany, NJ: Ferring Pharmaceuticals; January 2015 Page 4 of 6 CLINICAL POLICY Infertility Therapy 10. Pregnyl [Prescribing Information] Halle, Germany: Baxter Oncology GmbH; January 2015. 11. Ganirelix acetate [Prescribing Information]. Ravensburg, Germany: Vetter Pharma-Fertigung GmbH & Co. KG; March, 2016. 12. Cetrotide [Prescribing